Flecainide Induced Ventricular Tachycardia (Torsades de Pointes) JEROME THEVENIN, ANTOINE DA COSTA, FREDERIC ROCHE, CECILE ROMEYER, MARC MESSIER, and KARL ISAAZ From the Division of Cardiology, University Jean Monnet of Saint-Etienne, France
THEVENIN, J., ET AL.: Flecainide Induced Ventricular Tachycardia (Torsades de Pointes). This case report describes a 68-year-old woman presenting with flecainide induced syncope due to torsades de pointes (TP) ventricular tachycardia. Before TP onset, the QTc interval reached 680 ms without changes in QRS duration. None of the usual triggers were found. Prolongation of QT under fleca¨ınide is exceptional and the occurrence of TP without concurrent triggers has not been reported in the literature. (PACE 2003; 26:1907–1908) torsades de pointes, flecainide Introduction Torsades de pointes (TP) is a potentially lifethreatening polymorphic ventricular tachycardia characterized by a long QT interval, polymorphous QRS complexes with varying R-R intervals, and fluctuating QRS axis.1 Acquired TP, which is usually bradycardia dependent, occurs during electrolyte imbalance and is occasionally induced by antiarrhythmic agents.2 The risk of sudden death is linked to the degeneration of pause dependent TP to ventricular fibrillation (VF). This has been associated with structural heart disease.3 There have been several reports of TP induced by Class Ia and Class III antiarrhythmic drugs. Three cases were published in relation to Class Ic antiarrhythmic drug therapy.4−6 In these reports, the TPs are due to the interaction of flecainide with other drugs or metabolic disturbances.4−6 The following case report describes the first flecainide induced TP without associated interactions. Case Report A 68-year-old woman without familial history of sudden death was referred for atrial fibrillation (AF). The presence of symptoms like dyspnea and palpitation revealed the arrhythmia. A reference checkup performed by a cardiologist 1 year before the referral was considered normal and included a physical examination, 12-lead electrocardiogram (ECG), and echocardiography. At admittance, the ECG showed AF with normal QRS, normal QT and corrected QT (QT = 400 ms and QTc = 400 ms) and an absence of epsilon or delta waves (Fig. 1). These observations did not evidence preexcitation nor a Brugada syndrome. The mean heart rate was 60 beats/min. Laboratory data (including T3, T4, Address for reprints: Antoine Da Costa, M.D., Service de Cardiologie, Hopital Nord, Centre Hospitalier Universitaire de Saintˆ ˆ ´ ´ Etienne, 42055 Saint-Etienne CEDEX 2, France. Fax: (33) 47782-84-51; e-mail:
[email protected] Received December 16, 2002; accepted January 12, 2003.
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TSH) did not reveal abnormal or remarkable values. The left ventricular ejection fraction was normal (65%). The patient was prepared for an external electrical cardioversion with anticoagulant therapy and after 5 days, a transesophageal exploration excluded the presence of thrombi. The external anteroposterior cardioversion (360 J) was performed under general anesthesia and sinus rhythm restored. The patient was then started on flecainide (200 mg/day) and discharged. During the ECG recordings with a R-Test evolution, programmed 1 month after hospital discharge, the patient was admitted to the emergency room for a Stoke-Adams syncope. A second loss of consciousness occurred 1 hour later. Cardiovascular and physical examination were normal. Basal ECG was abnormal with a prolonged QT (QT = QTc = 520 ms, heart rate 60 beats/min) and negative T waves in the precordial leads (Fig. 2). Transthoracic echocardiography was negative. Biological analysis, including serum potassium and magnesium, illustrated no abnormality and there were no cardiac enzyme elevation. Holter analysis revealed 24 self-terminating TP with QT reaching 680 ms (Fig. 3) and two symptomatic, prolonged episodes. A relative sinus bradycardia of 45 beats/min was documented before TP onset. Due to the arrhythmic event and the presence of negative T waves, a cardiac angiography and a repeat transthoracic echocardiography were performed. Both were normal. Flecainide was withheld and 5 days later a pacemaker was implanted to prevent sinus dysfunction under antiarrhythmic medication. The patient was placed on atenolol (100 mg/day) therapy with a pacing rate programmed at 75 beats/min. After 7 months, the patient was still free of symptoms and atrial fibrillation has not recurred. Discussion TP usually occurs during electrolyte disturbances and is a proarrhythmia occasionally
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Figure 1. Initial electrocardiogram (ECG) with atrial fibrillation and normal QT (corrected QT = 400 ms).
associated with antiarrhythmic agents of the Ia and III Class.2 These drugs induce lengthen action potentials that can lead to early after depolarization resulting in QT prolongation and eventually TP.2 Exceptional cases of TP induced in the presence of flecainide have been previously described.4−6 In these published cases, however, several associ-
Figure 2. Abnormal basal electrocardiogram (ECG) with a prolonged QT (520 ms) and corrected QT (520 ms) at a mean heart rate of 60 beats/min.
Figure 3. One episode recorded during Holter monitoring showing prolonged QT (QT = 800 ms and corrected QT = 680 ms) with a typical self-terminating torsades de pointes (TP) (mean heart rate of 45 beats/min before TP onset).
ations may have contributed to the development of TP with fleca¨ınide: mosapride,5 or amiodarone interaction,6 and metabolic depletion.4 Analysis revealed moderate QT prolongation. This report describes the first case of TP induced by flecainide without associated interactions. It is possible that the flecainide induced a minor sinus dysfunction (45 beats/min) leading to a prolonged QT without QRS prolongation. These are conditions of early depolarization and acquired TP. This effect seems unusual, as flecainide usually prolongs QT intervals slightly, via increasing action potential duration, through the selective Ikr channel-blocking properties on ventricular myocytes. The occasional QT prolongation observed is thus primarily a result of increased QRS complex duration.7,8 Conclusion This case supports the view that fleca¨ınide acetate can prolong the QT interval without affecting the QRS interval, exceptionally inducing TP even in the absence of drugs or metabolic interactions.
References 1.
Dessertenne F. La tachycardie ventriculaire a` deux foyers oppos´es variables. Arch Mal Cœur 1966; 59:263–272. 2. Jackman WM, Friday KJ, Anderson JL, et al. The long QT syndromes: A critical review, new clinical observations and a unifying hypothesis. Prog Cardiovasc Dis 1988; 31:115– 172. 3. Da Costa A, Chalvidan T, Belounas A, et al. Predictive factors of ventricular fibrillation in pause dependent torsades de pointes associated with acquired long QT interval. J Card Electrophysiol 2000; 11:990–997. 4. Wickers F, Haissaguere M, Palussiere J. Prolongation and torsades
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de pointe induced by fleca¨ınide. One case. Arch Mal Coeur 1988; 81:1283–1285. 5. Ohki R, Takahashi M, Mizuno O, et al. Torsades de pointes ventricular tachycardia induced by mosapride and flecainide in the presence of hypokalemia. PACE 2001; 24:119–121. 6. Andrivet P, Beaslay V, Canh VD. Torsades de pointes with flecainideamiodarone therapy. Intensive Care Med 1990; 16:342–343. 7. Falk RH, Fogel RI. Flecainide. J Cardiovasc Electrophysiol 1994; 5:964–981. 8. Katritsis D, Rowland E, O’Nunain S, et al. Eur Heart J 1995; 16:1930– 1935.
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